Clean Area Classification

Purpose of Clean Area Classification

• Define Cleanliness Levels: Establish acceptable levels of particulate and microbial contamination.
• Regulatory Compliance: Meet standards set by regulatory bodies for sterile manufacturing.

Classification Standards

• ISO 14644-1: International standard for cleanrooms and associated controlled environments.
• EU GMP (European Union Good Manufacturing Practice): Provides guidelines for manufacturing medicinal products.
• FDA and USP Guidelines: US-specific regulations for sterile pharmaceutical production.

ISO Cleanroom Classifications

• ISO Class 5 (Class 100): Maximum of 3,520 particles ≥0.5 μm per cubic meter.
• ISO Class 7 (Class 10,000): Maximum of 352,000 particles ≥0.5 μm per cubic meter.
• ISO Class 8 (Class 100,000): Maximum of 3,520,000 particles ≥0.5 μm per cubic meter.

GMP Cleanroom Grades

• Grade A:

  • Highest level of cleanliness, for high-risk operations like filling and aseptic connections.

• Grade B:

  • Background environment for Grade A activities, such as the background for aseptic preparation and filling.

• Grade C:

  • Clean areas for less critical stages in sterile product manufacturing.

• Grade D:

  • Clean areas for less critical processes, such as handling of components after final cleaning.

Microbial Limits of Clean Area Classification

• Non-Viable Particles: Limits set for airborne particles based on cleanroom classification.
• Viable Microbial Counts:
  • Air Samples: Colony-forming units (CFUs) per cubic meter.
  • Surface Samples: CFUs per plate or swab area.

Monitoring and Compliance

• Environmental Monitoring Program:

  • Regular Testing: Scheduled monitoring of air and surfaces.
  • Trend Analysis: Evaluate data over time to detect deviations.

• Certification and Recertification:

  • Initial Qualification: Validate cleanroom performance upon setup.
  • Periodic Requalification: Regular re-testing to ensure ongoing compliance.

Cleanroom Design Considerations

• Airflow Patterns: Design to prevent turbulence and recirculation of particles.
• Room Pressurization: Positive pressure gradients from cleaner to less clean areas.
• Material and Personnel Entry: Use airlocks and gowning rooms to maintain pressure differentials.

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